Calcitonin gene-related peptide: 24-hour profile and responses to volume contraction and expansion in normal men.

Plasma immunoreactive calcitonin-gene related peptide (CGRP) concentrations were measured in 10 normal male subjects, aged 23-34 yr, who were studied under 3 separate conditions at intervals of at least 1 week. In phase 1, plasma CGRP concentrations were measured hourly for 24 h during normal activity; in phase 2, the CGRP response to diuretic-induced volume depletion and upright posture was measured over 3 h; in phase 3, the CGRP response to volume loading and supine posture was measured over 4 h. During phase 1, the mean 24-h plasma CGRP concentration averaged 30 +/- 16 pmol/L; hourly CGRP concentrations ranged from 25-37 pmol/L over 24 h and oscillated from 16% below to 27% above the mean 24-h CGRP value, changes that were highly significant (P = 0.005). The peaks were at 0600 and 0700 h, while the nadirs were at 1200 and 2000 h. No significant difference was found between fasting CGRP at 0800 h and levels taken 1, 2, and 3 h postprandially (P = 0.68). During phase 2 (volume depletion and upright) mean plasma CGRP rose significantly, going from a baseline of 42 +/- 8 pmol/L at 0800 h to a peak of 60 +/- 10 pmol/L at 1100 h (P = 0.0005). The percent CGRP increment was relatively small (26% to 42%) compared to the rise in PRA (518% to 1033%) and aldosterone concentrations (333% to 465%). Hematocrit increased from 40.5 +/- 0.7% to 45.8 +/- 0.7% (P = 0.0001) in phase 2, while serum osmolality did not change significantly. In phase 3 (volume loading and supine), plasma CGRP did not change significantly, while PRA and aldosterone concentrations fell significantly (P = 0.0001); neither serum osmolality nor hematocrit changed significantly. We conclude that plasma CGRP concentrations fluctuate spontaneously and significantly during the day, and rise in response to volume depletion. The reasons for the CGRP fluctuations seen over 24 h, which are not apparent from this study, may be related to changes in vascular volume or other as yet unidentified factors. These studies are consistent with the concept that CGRP, acting either directly or through the renin-aldosterone system, may have a role in regulating peripheral vascular tone or controlling vascular volume.

Cystic thyroid nodules. The dilemma of malignant lesions.

A retrospective study of 221 surgically resected thyroid nodules disclosed that 71 (32%) were cystic and 150 (68%) were solid lesions. Ultrasonography correctly characterized cystic nodules in all but one case. Comparing cystic and solid nodules, there were no differences in patient demographics (mean ages, 47.7 +/- 1.8 SEM vs 45.9 +/- 1.2 years; sex, 78% females both groups), the proportion that were solitary (39% vs 40%), or the nodule size (49% vs 47% greater than or equal to 2 cm in diameter). Of cystic thyroid lesions, 4% were simple cysts, 82% were degenerating benign adenomas or colloid nodules, and 14% were malignant compared with 23% of solid lesions that were malignant. Most cystic lesions (81%) contained bloody fluid. One benign true cyst was filled with thick brown fluid, while clear yellow fluid was repeatedly aspirated from one malignant cystic nodule. Malignant fine-needle aspiration cytology was the best predictor of cancer (100%). Much less predictable were signs of local compression or invasion (43%), a history of head or neck irradiation (33%), cyst recurrence after aspiration (29%), or an increase in the cystic nodule's size (7%). Indeterminate cytology identified malignancy with about half the frequency in cystic lesions as compared with solid nodules (13% vs 27%). The only false-negative fine-needle aspiration cytology occurred in a cystic lesion. In patients with cystic papillary cancers, needle aspirates contained insufficient material for diagnosis in 20% that occurred in no patient with solid papillary carcinoma. The sensitivities and specificities of fine-needle aspiration cytology for solid nodules were 100% and 55%, and for cystic nodules were 88% and 52%. Thus, cystic lesions are as likely as solid thyroid lesions to harbor a malignancy that cannot be predicted from the cyst's clinical characteristics or the patient's demographic data. Although fine-needle biopsy is the best predictor of malignancy in either cystic or solid thyroid lesions, it is slightly less reliable when a thyroid lesion is fluid filled rather than solid. We believe that most cysts not abolished by aspiration should be surgically excised.

Thyrotoxicosis. Results and risks of current therapy.

Effective therapy for thyrotoxicosis hinges on prompt recognition of the syndrome. When the diagnosis is suspected clinically but is not certain, the free thyroxine index is the most cost-effective test to order initially. The thyroidal radioactive iodine (123I) uptake is measured to differentiate Graves' disease from thyroiditis and other forms of thyrotoxicosis. Definitive therapy includes antithyroid drugs, iodine 131, and surgery. Patient preference has a large role in the final therapeutic choice.

Hemoptysis as the presenting manifestation of thyroid carcinoma. A case report.

An unusual case of a 61-year-old man who had hemoptysis as the major presenting manifestation of radiation-induced thyroid carcinoma is reported. The diagnosis was made by bronchoscopic removal of a polypoid lesion that was a direct extension of tumor through the trachea. Bronchoscopy is an effective and reliable means of establishing the diagnosis in this unusual subset of patients with thyroid carcinoma invading the trachea, and should be considered as the first diagnostic procedure in a patient with a thyroid mass and hemoptysis.

Thyroid function tests. Guidelines for interpretation in common clinical disorders.

While a wide variety of thyroid function tests are currently available, all are sometimes abnormal in patients without thyroid disease. To interpret test results properly, the clinician needs to be aware of factors altering thyroid function tests. In every instance, the clinician needs to begin by asking whether the patient is thyrotoxic or hypothyroid and then should order a test to substantiate or exclude the diagnosis. In this way, accurate and early diagnosis of thyroid dysfunction can be routinely established.

Sensitivity, specificity, and cost-effectiveness of the sensitive thyrotropin assay in the diagnosis of thyroid disease in ambulatory patients.

The sensitivity and specificity of two sensitive thyrotropin assays were compared with those of other standard thyroid function tests in 544 ambulatory subjects who were clinically euthyroid, thyrotoxic, or hypothyroid. Both sensitive thyrotropin assays had the highest sensitivity and specificity (95%/89% and 92%/95%), following by estimated free thyroxine (T4) level (82% and 94%), calculated free T4 index (78% and 93%), and free triiodothyronine index (86% and 88%). Sensitivity of the two thyrotropin assay kits in the diagnosis of thyrotoxicosis was 86% and 95%, and that in the diagnosis of hypothyroidism was 92% and 94%. Other tests were nearly as sensitive in the diagnosis of thyrotoxicosis but not hypothyroidism. A cost analysis of a testing strategy that used either total T4, free T4 index, or sensitive thyrotropin assay alone as the first-line thyroid test disclosed that to establish the patient's thyroid metabolic status would have cost $11,093, $14,536, and $24,902, respectively, using each test first. We suggest that, at current prices, routine use of the thyrotropin assay as a first-line test in ambulatory patients is not as cost-effective as the free T4 index.

Solitary thyroid nodule: diagnosis and management.

Thyroid nodules are common. Most are benign lesions since clinically important thyroid carcinoma is a relatively rare disease. The most sensitive and specific test for the diagnosis of thyroid cancer is fine-needle aspiration biopsy, but its diagnostic accuracy depends upon whether or not one excises all suspicious nodules, thus including them as correctly diagnosed. Nevertheless, fine-needle aspiration biopsy is the most sensitive, specific, and cost-effective test for thyroid cancer. Therapy depends upon the cause of the thyroid nodule.

Sensitive thyroid-stimulating hormone assays: clinical applications and limitations.

Sensitive TSH assays have important applications in various conditions, including the diagnosis of hypothyroidism and hyperthyroidism, monitoring thyroid hormone therapy and treated thyrotoxic patients, and evaluating thyroid dysfunction in nonthyroidal illnesses and pregnancy. Interpretation of the TSH value should be made with a clear understanding of its limitations. TSH may be inappropriately secreted by pituitary tumors and by pituitary dysfunction due to thyroxine resistance. At present, it is uncertain whether clinically euthyroid patients with autonomously functioning thyroid nodules, or with multinodular goiters, or patients taking thyroid hormone who have suppressed TSH values, are actually euthyroid at a cellular level. Other factors that affect TSH levels are the biologic variation in its secretion, the presence of heterophilic antibodies in a patient's serum, and various drugs. But perhaps the most important factor affecting the TSH assay is severe nonthyroidal illness in hospitalized patients. The new ultrasensitive TSH assay does not yet replace other thyroid function tests, but it is clearly emerging as an important means of screening patients for thyroid dysfunction, especially ambulatory patients without other serious illnesses. It can usually separate patients with thyroid dysfunction from euthyroid individuals. Good clinical assessment is always necessary, and other thyroid function tests are often needed. The sensitivity of these new TSH assays in the diagnosis of thyrotoxicosis and hypothyroidism is excellent; the specificity is not as good. Nonetheless, at present this test can be used in the initial diagnosis of thyroid dysfunction as outlined in Figure 2.(ABSTRACT TRUNCATED AT 250 WORDS)